Pediatric Sepsis Biomarker Risk Model Biomarkers and Estimation of Myocardial Dysfunction in Pediatric Septic Shock

Objectives: Sepsis-associated myocardial dysfunction is common in pediatric septic shock and negatively impacts outcomes. Early estimation of sepsis-associated myocardial dysfunction risk has the potential to inform clinical care and improve clinical trial design. The Pediatric Sepsis Biomarker Risk Model II is validated as a biomarker-based enrichment algorithm to discriminate children with septic shock with high baseline mortality probability. The objectives were to determine if Pediatric Sepsis Biomarker Risk Model biomarkers are associated with risk for sepsis-associated myocardial dysfunction in pediatric septic shock and to develop a biomarker-based model to reliably estimate sepsis-associated myocardial dysfunction risk.

Design: Secondary analysis of prospective cohort study.

Setting: Single-center, quaternary-care PICU.

Patients: Children less than 18 years old admitted to the PICU from 2003 to 2018 who had Pediatric Sepsis Biomarker Risk Model biomarkers measured for determination of Pediatric Sepsis Biomarker Risk Model II mortality probability and an echocardiogram performed within 48 hours of septic shock identification.

Interventions: None.

Measurements and main results: Pediatric Sepsis Biomarker Risk Model II mortality probability was calculated from serum biomarker concentrations and admission platelet count. Echocardiograms were reread by a single cardiologist blinded to Pediatric Sepsis Biomarker Risk Model II data, and sepsis-associated myocardial dysfunction was defined as left ventricular ejection fraction less than 45% for primary analyses. Multivariable logistic regression analyzed the association of Pediatric Sepsis Biomarker Risk Model II mortality probability with sepsis-associated myocardial dysfunction. Classification and regression tree methodology was employed to derive a Pediatric Sepsis Biomarker Risk Model biomarker-based model for sepsis-associated myocardial dysfunction. Thirty-two of 181 children with septic shock demonstrated sepsis-associated myocardial dysfunction. Pediatric Sepsis Biomarker Risk Model II mortality probability was independently associated with sepsis-associated myocardial dysfunction (odds ratio, 1.45; 95% CI, 1.17-1.81; p = 0.001). Modeling with Pediatric Sepsis Biomarker Risk Model biomarkers estimated sepsis-associated myocardial dysfunction risk with an area under the receiver operating characteristic curve of 0.90 (95% CI, 0.85-0.95). Upon 10-fold cross-validation, the derived model had a summary area under the receiver operating characteristic curve of 0.74. Model characteristics were similar when sepsis-associated myocardial dysfunction was defined by both low left ventricular ejection fraction and abnormal global longitudinal strain.

Conclusions: A newly derived Pediatric Sepsis Biomarker Risk Model biomarker-based model reliably estimates risk of sepsis-associated myocardial dysfunction in pediatric septic shock, but independent prospective validation is needed.